Iron Mobilization from Intact Ferritin: Effect of Differential Redox Activity of Quinone Derivatives

Abstract

Ferritins are nanocage proteins that sequester and concentrate excess free iron as ferric oxy-hydroxide biomineral in its central nanocavity and functions as cellular storehouse [1]. Although ferritin releases iron in a controlled fashion for various cellular metabolic activities, the mechanism of its release, in vivo, remains unclear and debatable. Reductive iron mobilization from the intact ferritin cage can be a reasonable pathway/possibility in vivo, due to the reducing nature of the cytosol. However, NADH, a physiological reducing agent was not sufficient to mobilize significant amount of ferritin iron, when used alone [2]. Therefore, the current work utilizes a series of quinone (as electron mediator), in conjugation with NADH, that differ in size, substituents and reduction potential, to facilitate the reductive iron mobilization, in vitro. Quinones are versatile electron mediators that facilitate important biological processes by undergoing both 1 and 2 electron transfer steps. Our result on structure-reactivity of quinone mediators highlight at-least two important findings: 1. Electron relay depends on midpoint potential (E1/2 ) value i.e. quinones with E1/2 values lying at a favorable range (not too close not too far) with respect to NADH exhibited better electron relay, 2. Iron release is dictated by molecular structure i.e. quinones with chelation sites releases higher amounts of iron, by reductive pathway. Further, the impact of in situ generated ROS viz. superoxide (O2 •), peroxide (H2O2 ) and intermediates (semiquinone) were analyzed and correlated with the kinetics of iron release. This quinone mediated iron mobilization can not only be exploited for iron removal during biological iron overload conditions but also provides insight towards plant/microbial iron acquisition processes to control their growth.